The presence of pharmaceutical compounds in water and soil has become an environmental concern. The aim of this study was to evaluate the performance of TiO2 nanofiber in the oxidation of the antibiotic tetracycline. TiO2 nanofiber was fabricated by electro-spinning method, and then was calcined at 560°C for 2 h. Central composite design (CCD) statistic model was used to optimize tetracycline concentration, time and pH for TiO2 catalyst. A tubular Pyrex glass reactor with diameter of 15 cm and height of 30 cm was designed and a 125W Philips HPLN lamp (UV, λ > 254 nm) was used as light source. Samples were measured by high-performance liquid chromatography (HPLC). Equation of model suggests a direct relationship between pH and time with efficiency of tetracycline removal. The observations indicated that time is the most significant (scaled estimate = + 28.04) parameter in efficiency of tetracycline removal. The application of response surface methodology yielded the equation of Y = 65.82 + 5.74 pH + 28.04 time + (-3.07)(pH)2 + (-6.6)(time)2, with R2 = 0.986 which represents good reliability of model. Based on the response surface plots optimum conditions for degradation of tetracycline with maximum efficiency of around 95% was attained. These conditions are as follow; concentration: 50 mg/l, pH= 8.3, time= 15 min.